The role of the oral spirochetes in the etiology of periodontal disease is poorly defined. Since associations between the severity of periodontal disease and the presence of the organisms have been made by a number of investigators, there is evidence that the spirochetes play a role in the disease process. Oral spirochetes populate the surface of subgingival plaque and are in an excellent location to interact with host inflammatory cells. Furthermore, non-oral spirochetes (e.g., Treponema pallidum) are known to suppress cell-mediated immunity despite the presence of high titers of anti-spirochete antibodies in the circulation. Since oral spirochetes are morphologically and antigenically related, they may also share immune properties. This proposal will examine differences in immune function between minimally diseased subjects (healthy volunteers) and periodontal patients. These studies will examine: (1) the levels of circulating antibodies to oral spirochetes using the micro-ELISA technique; (2) the blastogenic response of lymphocytes to spirochete preparations; and, (3) the immunomodulation by spirochetes of in vitro lymphocyte blastogenesis and immunoglobulin synthesis. This study is unique since we will utilize clinical isolates of oral spirochetes associated with various forms of periodontal disease, rather than employ laboratory strains which have been subcultured for up to thirty years.